The enzyme hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1; also referred to as HSD3B and HSDB3) catalyzes the conversion of 3-hydroxy-5-ene-steroids [e.g., dehydroepiandrosterone (DHEA) and pregnenolone] to 3-oxo-4-ene-steroids (androstenedione and progesterone, respectively). A single, dimeric HSD3B1 protein contains both enzyme activities. The HSD3B1 gene is expressed predominantly in mammary gland tissue, and also is expressed in placenta and skin. At the subcellular level, HSD3B1 is located in the endoplasmic reticulum and the mitochondrial membrane. During human pregnancy, the placental enzyme catalyzes conversion of pregnenolone to progesterone, which maintains the uterus in a quiescent state. Near term, however, the fetal zone adrenal gland produces large amounts (200 mg/day) of DHEA. Because the fetal adrenal gland lacks significant HSD3B1 activity, the placental enzyme converts the fetal DHEA to androstenedione. Androstenedione in turn is converted by placental aromatase and 17-hydroxysteroid dehydrogenase to estradiol, which participates in the cascade of events that initiates labor in humans. Other substrates for HSD3B1 include 17-hydroxypregnenolone and androst-5-ene-3-B,17B-diol. The HSD3B1 enzyme also is selectively expressed in human breast tumors, prostate tumors, and choriocarcinomas, where it catalyzes the first step in the conversion of circulating DHEA to, estradiol or testosterone to promote tumor growth.
Congenital deficiency of HSD3B1 activity causes severe depletion of steroid formation and frequently is lethal early in life. The classical form of this disease includes the association of severe salt-losing adrenal insufficiency and ambiguity of external genitalia in both sexes.